Fate mapping of single NK cells identifies a type 1 innate lymphoid-like lineage that bridges innate and adaptive recognition of viral infection [scRNAseq_Ly49H+_NK_retrogenic_spleen]. Fate mapping of single NK cells identifies a type 1 innate lymphoid-like lineage that bridges innate and adaptive recognition of viral infection [scRNAseq_Ly49H+_NK_retrogenic_spleen]

Upon viral infection, NK cells expressing certain germline-encoded receptors are selected, expanded and maintained in an adaptive-like manner. Currently, these are thought to differentiate along a common pathway. However, by fate mapping of single NK cells upon murine cytomegalovirus (MCMV) infection, we identified two distinct NK cell lineages that contributed to adaptive-like responses. One was equivalent to conventional NK (cNK) cells while the other was transcriptionally similar to type 1 innate lymphoid cells (ILC1s). ILC1-like NK cells showed splenic-residency and strong cytokine production but also recognized and killed MCMV-infected cells, guided by activating receptor Ly49H. Moreover, they induced clustering of conventional type 1 dendritic cells and facilitated antigen-specific T cell priming early during MCMV infection, which depended on Ly49H and the NK cell-intrinsic expression of transcription factor Batf3. Thereby, ILC1-like NK cells bridge innate and adaptive viral recognition and unite critical features of cNK cells and ILC1s. Overall design: One mRNA profile of total Ly49H+ NK cells from retrogenic spleen.当机体遭遇病毒感染时，表达特定种系编码受体的自然杀伤细胞（Natural Killer cells, NK细胞）会以类适应性免疫的方式被选择、扩增并维持存活。目前学界普遍认为此类细胞沿单一共同通路完成分化。然而本研究通过对小鼠巨细胞病毒（murine cytomegalovirus, MCMV）感染后的单个NK细胞进行命运图谱分析，鉴定出了两种可介导类适应性免疫应答的不同NK细胞谱系。其中一类与常规NK细胞（conventional NK, cNK）功能表型一致，而另一类在转录组特征上与1型固有淋巴细胞（type 1 innate lymphoid cells, ILC1s）高度相似。类ILC1 NK细胞具备脾脏驻留特性，可强力分泌细胞因子，同时能够通过活化性受体Ly49H识别并杀伤MCMV感染的宿主细胞。此外，在MCMV感染早期，此类细胞可诱导1型常规树突状细胞（conventional type 1 dendritic cells）聚集，并促进抗原特异性T细胞启动活化，这一调控过程依赖于Ly49H受体以及NK细胞内源性转录因子Batf3的表达。由此，类ILC1 NK细胞架起了固有免疫与适应性抗病毒识别之间的桥梁，同时兼具常规NK细胞与ILC1的关键功能特征。实验整体设计：获取自逆转录基因修饰脾脏的全部Ly49H阳性NK细胞的1组mRNA表达谱。